There are a number of unresolved basic science and clinical issues in retinoblastoma and uveal melanoma which can be elucidated using somatic cell hybridization techniques. In all human cancers the nature of tumor antigens, their specificity; allogeneic, primary, and metastatic tumor cross-reactivity; and rate of antigenic modulation are unclear. Monoclonal antibody studies in eye tumors can be used as a model to delineate the nature of human tumor-associated antigens; clinially their efficacy for diagnosis and therapy of metastatic and intraocular tumors will be studied. We have previously developed monoclonal antibodies directed against antigens present on uveal melanoma and retinoblastoma cells. We wish to further characterize these antigens, and select and develop those hybridoma produced antibodies which have sufficient allogeneic tumor-associated cross-reactivity and specificity for in vitro and in vivo diagnosis and therapy. It can be difficult to correctly diagnose extraocular retinoblastomas and our ability to predict the prognosis of patients whose eyes are treated with non-enucleation modalities is limited. Monoclonal antibodies will be used to develop in vitro immunoperoxidase and solid phase radioimmunoassays which may increase our diagnostic and prognostic accuracy. In both retinoblastoma and uveal melanoma patients metastatic disease is usually detected at a stage when it is almost always fatal. In vivo radionucleide scans will be performed using different imaging and isotope techniques with various anti-tumor antibody, Fab or F(ab)2 fragments to detect early metastatic and later intraocular tumors. This may allow us to diagnose and treat widespread or intraocular disease at an earlier stage. Therapeutically we will study in animals and humans the efficacy of hybridoma products conjugated various toxins to specifically treat metastases. It is conceivable that these monoclonal antibody-toxin conjugates may be more effective for delivery of toxins to tumor cells with lesser non-specific morbidity than is possible with currently available chemotherapy protocols. These conjugates will be used to initially treat metastatic retinoblastomas and uveal melanomas; potentially they might also have intraocular application.